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感染甲型H1N1流感大流行病毒(A(H1N1)pdm09)的孕妇表现出与疾病严重程度相关的不同免疫反应。

Pregnant women infected with pandemic influenza A(H1N1)pdm09 virus showed differential immune response correlated with disease severity.

作者信息

Periolo N, Avaro M, Czech A, Russo M, Benedetti E, Pontoriero A, Campos A, Peralta L Martinez, Baumeister E

机构信息

National Influenza Centre PAHO/WHO, Laboratorio Nacional de Referencia de Influenza y Virus Respiratorios, Servicio Virosis Respiratorias, Departamento Virología, Instituto Nacional de Enfermedades Infecciosas, ANLIS "Carlos G. Malbrán", Buenos Aires, Argentina.

National Influenza Centre PAHO/WHO, Laboratorio Nacional de Referencia de Influenza y Virus Respiratorios, Servicio Virosis Respiratorias, Departamento Virología, Instituto Nacional de Enfermedades Infecciosas, ANLIS "Carlos G. Malbrán", Buenos Aires, Argentina.

出版信息

J Clin Virol. 2015 Mar;64:52-8. doi: 10.1016/j.jcv.2015.01.009. Epub 2015 Jan 13.

Abstract

BACKGROUND

During pregnancy, immunological and hormonal alterations place women at increased risk for influenza-related severe illnesses including hospitalization and death. Although A(H1N1) pdm09 infection resulted in increased disease severity in pregnant women, the precise mechanisms responsible for this risk have yet to be established.

OBJECTIVES

The present study was aimed to investigate the role of host chemokines and cytokine profiles in A(H1N1) pdm09 infection regarding disease severity in pregnant women.

STUDY DESIGN

This retrospective survey examined 41 pregnant women with confirmed A(H1N1) pdm09 infection. Of them, 12 died (D), 29 survived (S), and 17 remained uninfected and served as controls (C). Antiviral response was evaluated for IFN-β expression and gene expression profiles of cytokines (TNF-α, IL-6, IL-12, TGF-β) and chemokines (IL-8, RANTES, MCP-1, IP-10), and the viral Matrix (M1) gene was quantified and normalized using the housekeeping gene product β-actin mRNA.

RESULTS

Higher IL-8 and TNF-α mRNA expression were found in D and S compared with C, while IL-6 showed higher expression in D. Interestingly, these results were associated with a decrease in the anti-inflammatory response of TGF-β mRNA and IFN-β. These alterations would lead to an imbalance in the immune response of those patients.

CONCLUSIONS

Pregnancy-related reductions in IFN-β and TGF-β expression levels and elevated levels of pro-inflammatory cytokines could explain the increased severity of infection and death of pregnant women. These findings may help improve the understanding of the high susceptibility and disease severity to influenza virus infection during pregnancy.

摘要

背景

在孕期,免疫和激素变化使女性患流感相关重症疾病(包括住院和死亡)的风险增加。尽管甲型H1N1流感病毒(A(H1N1)pdm09)感染导致孕妇疾病严重程度增加,但造成这种风险的确切机制尚未明确。

目的

本研究旨在探讨宿主趋化因子和细胞因子谱在A(H1N1)pdm09感染中对孕妇疾病严重程度的作用。

研究设计

这项回顾性调查研究了41例确诊为A(H1N1)pdm09感染的孕妇。其中,12例死亡(D组),29例存活(S组),17例未感染作为对照组(C组)。评估抗病毒反应的指标包括IFN-β表达、细胞因子(TNF-α、IL-6、IL-12、TGF-β)和趋化因子(IL-8、RANTES、MCP-1、IP-10)的基因表达谱,同时使用管家基因产物β-肌动蛋白mRNA对病毒基质(M1)基因进行定量和标准化。

结果

与C组相比,D组和S组中IL-8和TNF-α的mRNA表达更高,而IL-6在D组中表达更高。有趣的是,这些结果与TGF-β mRNA和IFN-β抗炎反应的降低有关。这些改变会导致这些患者免疫反应失衡。

结论

孕期IFN-β和TGF-β表达水平降低以及促炎细胞因子水平升高可解释孕妇感染严重程度增加及死亡情况。这些发现可能有助于增进对孕期流感病毒感染高易感性和疾病严重程度的理解。

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